Our laboratory, as well as others, has demonstrated abnormalities in brain structure and function associated with breast cancer chemotherapy, most consistently in the prefrontal cortex. The prefrontal cortex is critical for skills such as multi-tasking, attention, processing speed and memory; skills that are often impaired in patients who have undergone breast cancer chemotherapy. Because prefrontal cortex changes have also been observed in patients prior to chemotherapy treatment as well as in those treated with radiation and/or hormonal blockade, the specific effects of chemotherapy on prefrontal cortex remain unclear. It is also currently unknown why some patients treated with chemotherapy show improvement in cognitive function over time while others do not. The proposed research will examine prefrontal cortex structure and function as well as cognitive status in 50 patients with primary breast cancer scheduled for chemotherapy. These patients will be evaluated across the treatment course, from pre-surgery to 12 months post-chemotherapy. We will compare the chemotherapy-treated group to 50 patients who do not receive chemotherapy and to 50 healthy females who are all assessed at the same time intervals as the chemotherapy-treated group. We will utilize non-invasive neuroimaging (MRI) methods to measure prefrontal cortex volume and functional activation in combination with neuropsychological measures of executive function, memory, processing speed and attention. We will also explore possible predictors of individual outcome such as demographic, disease, psychiatric and treatment factors. Increasing our understanding regarding the neurobiologic mechanisms underlying chemotherapy-related cognitive impairments may improve identification of patients at highest risk for cognitive deficit and aid the development of treatments for these impairments. PUBLIC HEALTH RELEVANCE: A significant proportion of women who receive chemotherapy for breast cancer will experience long- term problems with brain function, such as thinking, memory and attention that reduce quality of life and extend disease-related disability. The proposed study aims to improve our understanding regarding the brain changes that occur during breast cancer chemotherapy. This research is highly relevant to breast cancer, one of the most common public health problems, affecting 1 in 8 women.